title: Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.
abstract: Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways.
authors.affiliation: CNRS, UMR 6290, Institut Génétique et Développement de Rennes, Rennes, France; Faculté de Médecine, SFR Biosit, Université Rennes 1, Rennes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Gillard
authors.forename: Edouard
authors.initials: E
authors.lastname: Cadieu
authors.forename: Clotilde
authors.initials: C
authors.lastname: De Brito
authors.forename: Jérôme
authors.initials: J
authors.lastname: Abadie
authors.forename: Béatrice
authors.initials: B
authors.lastname: Vergier
authors.forename: Patrick
authors.initials: P
authors.lastname: Devauchelle
authors.forename: Frédérique
authors.initials: F
authors.lastname: Degorce
authors.forename: Stephane
authors.initials: S
authors.lastname: Dréano
authors.forename: Aline
authors.initials: A
authors.lastname: Primot
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dorso
authors.forename: Marie
authors.initials: M
authors.lastname: Lagadic
authors.forename: Francis
authors.initials: F
authors.lastname: Galibert
authors.forename: Benoit
authors.initials: B
authors.lastname: Hédan
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Galibert
authors.forename: Catherine
authors.initials: C
authors.lastname: André
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D009363:Neoplasm Proteins
keywords: dog model; epidemiology; genetics; his-tology; melanomas; non-UV pathways; somatic mutations